Investigation of somatic CNVs in brains of synucleinopathy cases using targeted SNCA analysis and single cell sequencing
Synucleinopathies are mostly sporadic neurodegenerative disorders of partly unexplained aetiology, and include Parkinson’s disease (PD) and multiple system atrophy (MSA). We have further investigated our recen...Acta Neuropathologica Communications 2019 7:219Impaired β-glucocerebrosidase activity and processing in frontotemporal dementia due to progranulin mutations
Loss-of-function mutations in progranulin (GRN) are a major autosomal dominant cause of frontotemporal dementia. Most pathogenic GRN mutations result in progranulin haploinsufficiency, which is thought to cause f...Acta Neuropathologica Communications 2019 7:218Sleep deprivation of rats increases postsurgical expression and activity of L-type calcium channel in the dorsal root ganglion and slows recovery from postsurgical pain
Perioperative sleep disturbance is a risk factor for persistent pain after surgery. Clinical studies have shown that patients with insufficient sleep before and after surgery experience more intense and long-l...Acta Neuropathologica Communications 2019 7:217Triiodothyronine modulates neuronal plasticity mechanisms to enhance functional outcome after stroke
The development of new therapeutic approaches for stroke patients requires a detailed understanding of the mechanisms that enhance recovery of lost neurological functions. The efficacy to enhance homeostatic m...Acta Neuropathologica Communications 2019 7:216Characterization of lysosomal proteins Progranulin and Prosaposin and their interactions in Alzheimer’s disease and aged brains: increased levels correlate with neuropathology
Progranulin (PGRN) is a protein encoded by the GRN gene with multiple identified functions including as a neurotrophic factor, tumorigenic growth factor, anti-inflammatory cytokine and regulator of lysosomal f...Acta Neuropathologica Communications 2019 7:215Comparative profiling of the synaptic proteome from Alzheimer’s disease patients with focus on the APOE genotype
Degeneration of synapses in Alzheimer’s disease (AD) strongly correlates with cognitive decline, and synaptic pathology contributes to disease pathophysiology. We recently observed that the strongest genetic r...Acta Neuropathologica Communications 2019 7:214Organotypic slice culture model demonstrates inter-neuronal spreading of alpha-synuclein aggregates
Here we describe the use of an organotypic hippocampal slice model for studying α-synuclein aggregation and inter-neuronal spreading initiated by microinjection of pre-formed α-synuclein fibrils (PFFs). PFF in...Acta Neuropathologica Communications 2019 7:213Polarizing receptor activation dissociates fibroblast growth factor 2 mediated inhibition of myelination from its neuroprotective potential
Fibroblast growth factor (FGF) signaling contributes to failure of remyelination in multiple sclerosis, but targeting this therapeutically is complicated by its functional pleiotropy. We now identify FGF2 as a...Acta Neuropathologica Communications 2019 7:212Bi-allelic mutations in uncoordinated mutant number-45 myosin chaperone B are a cause for congenital myopathy
Congenital myopathies (CM) form a genetically heterogeneous group of disorders characterized by perinatal muscle weakness. Here, we report an 11-year old male offspring of consanguineous parents of Lebanese or...Acta Neuropathologica Communications 2019 7:211Methylene blue inhibits Caspase-6 activity, and reverses Caspase-6-induced cognitive impairment and neuroinflammation in aged mice
Activated Caspase-6 (Casp6) is associated with age-dependent cognitive impairment and Alzheimer disease (AD). Mice expressing human Caspase-6 in hippocampal CA1 neurons develop age-dependent cognitive deficits...Acta Neuropathologica Communications 2019 7:210Glycine-alanine dipeptide repeats spread rapidly in a repeat length- and age-dependent manner in the fly brain
Hexanucleotide repeat expansions of variable size in C9orf72 are the most prevalent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Sense and antisense transcripts of the expansions ar...Acta Neuropathologica Communications 2019 7:209Cellular alterations identified in pluripotent stem cell-derived midbrain spheroids generated from a female patient with progressive external ophthalmoplegia and parkinsonism who carries a novel variation (p.Q811R) in the POLG1 gene
Variations in the POLG1 gene encoding the catalytic subunit of the mitochondrial DNA polymerase gamma, have recently been associated with Parkinson’s disease (PD), especially in patients diagnosed with progres...Acta Neuropathologica Communications 2019 7:208Tau pathology in the medial temporal lobe of athletes with chronic traumatic encephalopathy: a chronic effects of neurotrauma consortium study
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative condition associated with repetitive traumatic brain injury (rTBI) seen in contact-sport athletes and military personnel. The medial te...Acta Neuropathologica Communications 2019 7:207Aldehyde dehydrogenase 2 activity and aldehydic load contribute to neuroinflammation and Alzheimer’s disease related pathology
Aldehyde dehydrogenase 2 deficiency (ALDH2*2) causes facial flushing in response to alcohol consumption in approximately 560 million East Asians. Recent meta-analysis demonstrated the potential link between AL...Acta Neuropathologica Communications 2019 7:190Regulation of microglial TMEM119 and P2RY12 immunoreactivity in multiple sclerosis white and grey matter lesions is dependent on their inflammatory environment
Multiple Sclerosis (MS) is the most common cause of acquired neurological disability in young adults, pathologically characterized by leukocyte infiltration of the central nervous system, demyelination of the ...Acta Neuropathologica Communications 2019 7:206Molecular signature of different lesion types in the brain white matter of patients with progressive multiple sclerosis
To identify pathogenetic markers and potential drivers of different lesion types in the white matter (WM) of patients with progressive multiple sclerosis (PMS), we sequenced RNA from 73 different WM areas. Com...Acta Neuropathologica Communications 2019 7:205Magnetic resonance imaging brain atrophy assessment in primary age-related tauopathy (PART)
Alzheimer disease (AD) is a neurodegenerative disorder characterized pathologically by the accumulation of amyloid-beta (Aβ) plaques and tau neurofibrillary tangles (NFTs). Recently, primary age-related tauopa...Acta Neuropathologica Communications 2019 7:204Tau- but not Aß -pathology enhances NMDAR-dependent depotentiation in AD-mouse models
Many mouse models of Alzheimer’s disease (AD) exhibit impairments in hippocampal long-term-potentiation (LTP), seemingly corroborating the strong correlation between synaptic loss and cognitive decline reporte...Acta Neuropathologica Communications 2019 7:202Single-nucleus chromatin accessibility reveals intratumoral epigenetic heterogeneity in IDH1 mutant gliomas
The presence of genome-wide DNA hypermethylation is a hallmark of lower grade gliomas (LGG) with isocitrate dehydrogenase (IDH) mutations. Further molecular classification of IDH mutant gliomas is defined by t...Acta Neuropathologica Communications 2019 7:201Kinesin light chain-1 serine-460 phosphorylation is altered in Alzheimer’s disease and regulates axonal transport and processing of the amyloid precursor protein
Damage to axonal transport is an early pathogenic event in Alzheimer’s disease. The amyloid precursor protein (APP) is a key axonal transport cargo since disruption to APP transport promotes amyloidogenic proc...Acta Neuropathologica Communications 2019 7:200The transcriptional coactivator and histone acetyltransferase CBP regulates neural precursor cell development and migration
CREB (cyclic AMP response element binding protein) binding protein (CBP, CREBBP) is a ubiquitously expressed transcription coactivator with intrinsic histone acetyltransferase (KAT) activity. Germline mutation...Acta Neuropathologica Communications 2019 7:199Epidemiological pathology of Aβ deposition in the ageing brain in CFAS: addition of multiple Aβ-derived measures does not improve dementia assessment using logistic regression and machine learning approaches
Aβ-amyloid deposition is a key feature of Alzheimer’s disease, but Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessment, based on neuritic plaque density, shows a limited relationships...Acta Neuropathologica Communications 2019 7:198A metastable subproteome underlies inclusion formation in muscle proteinopathies
Protein aggregation is a pathological feature of neurodegenerative disorders. We previously demonstrated that protein inclusions in the brain are composed of supersaturated proteins, which are abundant and agg...Acta Neuropathologica Communications 2019 7:197KCC2 expression levels are reduced in post mortem brain tissue of Rett syndrome patients
Rett Syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the Methyl CpG binding protein 2 (MECP2) gene. Deficient K+-Cl—co-transporter 2 (KCC2) expression is suggested to play a key role in the...Acta Neuropathologica Communications 2019 7:196Secernin-1 is a novel phosphorylated tau binding protein that accumulates in Alzheimer’s disease and not in other tauopathies
We recently identified Secernin-1 (SCRN1) as a novel amyloid plaque associated protein using localized proteomics. Immunohistochemistry studies confirmed that SCRN1 was present in plaque-associated dystrophic ...Acta Neuropathologica Communications 2019 7:195The amyloid-β degradation intermediate Aβ34 is pericyte-associated and reduced in brain capillaries of patients with Alzheimer’s disease
An impairment of amyloid β-peptide (Aβ) clearance is suggested to play a key role in the pathogenesis of sporadic Alzheimer’s disease (AD). Amyloid degradation is mediated by various mechanisms including fragm...Acta Neuropathologica Communications 2019 7:194Luminescent conjugated oligothiophenes distinguish between α-synuclein assemblies of Parkinson’s disease and multiple system atrophy
Synucleinopathies [Parkinson’s disease with or without dementia, dementia with Lewy bodies and multiple system atrophy] are neurodegenerative diseases that are defined by the presence of filamentous α-synuclei...Acta Neuropathologica Communications 2019 7:193A post-translational modification signature defines changes in soluble tau correlating with oligomerization in early stage Alzheimer’s disease brain
Tau is a microtubule-binding protein that can receive various post-translational modifications (PTMs) including phosphorylation, methylation, acetylation, glycosylation, nitration, sumoylation and truncation. ...Acta Neuropathologica Communications 2019 7:192Mosaic PTEN alteration in the neural crest during embryogenesis results in multiple nervous system hamartomas
The contribution of mosaic alterations to tumors of the nervous system and to non-malignant neurological diseases has been unmasked thanks to the development of Next Generation Sequencing (NGS) technologies. W...Acta Neuropathologica Communications 2019 7:191Circadian sleep/wake-associated cells show dipeptide repeat protein aggregates in C9orf72-related ALS and FTLD cases
Motor-, behavior- and/or cognition-related symptoms are key hallmarks in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) with TDP-43 pathology (FTLD-TDP), respect...Acta Neuropathologica Communications 2019 7:189Immune landscapes associated with different glioblastoma molecular subtypes
Recent work has highlighted the tumor microenvironment as a central player in cancer. In particular, interactions between tumor and immune cells may help drive the development of brain tumors such as glioblast...Acta Neuropathologica Communications 2019 7:203An AARS variant as the likely cause of Swedish type hereditary diffuse leukoencephalopathy with spheroids
Swedish type Hereditary Diffuse Leukoencephalopathy with Spheroids (HDLS-S) is a severe adult-onset leukoencephalopathy with the histopathological hallmark of neuraxonal degeneration with spheroids, described ...Acta Neuropathologica Communications 2019 7:188Blood brain barrier leakage is not a consistent feature of white matter lesions in CADASIL
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic paradigm of small vessel disease (SVD) caused by NOTCH3 mutations that stereotypically lead to the...Acta Neuropathologica Communications 2019 7:187Attenuation of neuroinflammation reverses Adriamycin-induced cognitive impairments
Numerous clinical studies have established the debilitating neurocognitive side effects of chemotherapy in the treatment of breast cancer, often referred as chemobrain. We hypothesize that cognitive impairment...Acta Neuropathologica Communications 2019 7:186Mapping actionable pathways and mutations in brain tumours using targeted RNA next generation sequencing
Many biology-based precision drugs are available that neutralize aberrant molecular pathways in cancer. Molecular heterogeneity and the lack of reliable companion diagnostic biomarkers for many drugs makes tar...Acta Neuropathologica Communications 2019 7:185Exosome release and neuropathology induced by α-synuclein: new insights into protective mechanisms of Drp1 inhibition
Targeting alpha-synuclein (α-syn) as a therapeutic strategy for Parkinson’s disease (PD) has been intensively pursued largely due to its well-recognized pathogenic role. Since its discovery as the first famili...Acta Neuropathologica Communications 2019 7:184Alzheimer’s disease tau is a prominent pathology in LRRK2 Parkinson’s disease
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease (PD). While the clinical presentation of LRRK2 mutation carriers is similar to that of idiopathic PD (iP...Acta Neuropathologica Communications 2019 7:183DNA repair deficiency and senescence in concussed professional athletes involved in contact sports
Mild traumatic brain injury (mTBI) leads to diverse symptoms including mood disorders, cognitive decline, and behavioral changes. In some individuals, these symptoms become chronic and persist in the long-term...Acta Neuropathologica Communications 2019 7:182Improved risk-stratification for posterior fossa ependymoma of childhood considering clinical, histological and genetic features – a retrospective analysis of the HIT ependymoma trial cohort
Risk stratification of children with ependymomas of the posterior fossa in current therapeutic protocols is mainly based on clinical criteria. We aimed to identify independent outcome predictors for this disea...Acta Neuropathologica Communications 2019 7:181Increased soluble amyloid-beta causes early aberrant brain network hypersynchronisation in a mature-onset mouse model of amyloidosis
Alzheimer’s disease (AD) is the most common form of dementia in the elderly. According to the amyloid hypothesis, the accumulation and deposition of amyloid-beta (Aβ) peptides play a key role in AD. Soluble Aβ...Acta Neuropathologica Communications 2019 7:180Correction to: c-MYC overexpression induces choroid plexus papillomas through a T-cell mediated inflammatory mechanism
In the original version of this article [1], there was 1 error in the affiliation of the European Institute of Oncology (affiliation 3). In this correction article the updated affiliation is shown for clarific...Acta Neuropathologica Communications 2019 7:179The original article was published in Acta Neuropathologica Communications 2019 7:95Different aspects of Alzheimer’s disease-related amyloid β-peptide pathology and their relationship to amyloid positron emission tomography imaging and dementia
Alzheimer’s disease (AD)-related amyloid β-peptide (Aβ) pathology in the form of amyloid plaques and cerebral amyloid angiopathy (CAA) spreads in its topographical distribution, increases in quantity, and unde...Acta Neuropathologica Communications 2019 7:178N368-Tau fragments generated by legumain are detected only in trace amount in the insoluble Tau aggregates isolated from AD brain
Intraneuronal insoluble inclusions made of Tau protein are neuropathological hallmarks of Alzheimer Disease (AD). Cleavage of Tau by legumain (LGMN) has been proposed to be crucial for aggregation of Tau into ...Acta Neuropathologica Communications 2019 7:177- Acta Neuropathologica Communications 2019 7:176
The level of activity of the alternative lengthening of telomeres correlates with patient age in IDH-mutant ATRX-loss-of-expression anaplastic astrocytomas
All cancer cells need to maintain functional telomeres to sustain continuous cell division and proliferation. In human diffuse gliomas, functional telomeres are maintained due either to reactivation of telomer...Acta Neuropathologica Communications 2019 7:175Microglial motility in Alzheimer’s disease and after Aβ42 immunotherapy: a human post-mortem study
Microglial function is highly dependent on cell motility, with baseline motility required for homeostatic surveillance activity and directed motility to migrate towards a source of injury. Experimental evidenc...Acta Neuropathologica Communications 2019 7:174Region-specific interneuron demyelination and heightened anxiety-like behavior induced by adolescent binge alcohol treatment
Adolescent binge drinking represents a major public health challenge and can lead to persistent neurological and mental conditions, but the underlying pathogenic mechanisms remain poorly understood. Using a mo...Acta Neuropathologica Communications 2019 7:173Chemokines modulate the tumour microenvironment in pituitary neuroendocrine tumours
Non-tumoural cells within the tumour microenvironment (TME) influence tumour proliferation, invasiveness and angiogenesis. Little is known about TME in pituitary neuroendocrine tumours (PitNETs). We aimed to c...Acta Neuropathologica Communications 2019 7:172In vivo detection of tau fibrils and amyloid β aggregates with luminescent conjugated oligothiophenes and multiphoton microscopy
The detection of amyloid beta deposits and neurofibrillary tangles, both hallmarks of Alzheimer’s disease (AD), is key to understanding the mechanisms underlying these pathologies. Luminescent conjugated oligo...Acta Neuropathologica Communications 2019 7:171Synergistic toxicity in an in vivo model of neurodegeneration through the co-expression of human TDP-43M337V and tauT175D protein
Although it has been suggested that the co-expression of multiple pathological proteins associated with neurodegeneration may act synergistically to induce more widespread neuropathology, experimental evidence...Acta Neuropathologica Communications 2019 7:170
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